tbuckley/cabot-search huggingface dataset:
Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “<scp>Flip‐Flop</scp>” phenomenon)
Authors: Svenja Müller, Thomas Welchowski, Matthias Schmid, Laura Maintz, Nadine Herrmann, Dagmar Wilsmann‐Theis, Thorben Royeck, Regina Havenith, Thomas Bieber
Journal: Allergy (2023)

Abstract Background Atopic dermatitis (AD) and psoriasis vulgaris (PV) are almost mutually exclusive diseases with different immune polarizations, mechanisms and therapeutic targets. Switches to the other disease (“Flip‐Flop” [FF] phenomenon) can occur with or without systemic treatment and are often referred to as paradoxical reactions under biological therapy. Methods The objective was to develop a diagnostic algorithm by combining clinical criteria of AD and PV to identify FF patients. The algorithm was prospectively validated in patients enrolled in the CK‐CARE registry in Bonn, Germany. Afterward, algorithm refinements were implemented based on machine learning. Results Three hundred adult Caucasian patients were included in the validation study ( n = 238 with AD, n = 49 with PV, n = 13 with FF; mean age 41.2 years; n = 161 [53.7%] female). The total FF scores of the PV and AD groups differed significantly from the FF group in the validation data ( p &lt; .001). The predictive mean generalized Youden‐Index of the initial model was 78.9% [95% confidence interval 72.0%–85.6%] and the accuracy was 89.7%. Disease group‐specific sensitivity was 100% (FF), 95.0% (AD), and 61.2% (PV). The specificity was 89.2% (FF), 100% (AD), and 100% (PV), respectively. Conclusion The FF algorithm represents the first validated tool to identify FF patients.
Ginsenoside Rg3 endows liposomes with prolonged blood circulation and reduced accelerated blood clearance
Authors: Jiaxuan Xia, Chen Chen, Meichen Dong, Ying Zhu, Anni Wang, Shiyi Li, Ru Zhang, Chunbo Feng, Xinnan Jiang, Xinchun Xu, Jianxin Wang
Journal: Journal of Controlled Release (2023)
Conductive electrospun polymer improves stem cell-derived cardiomyocyte function and maturation
Authors: Gisselle Gonzalez, Aileena C. Nelson, Alyssa R. Holman, Alexander J. Whitehead, Erin LaMontagne, Rachel Lian, Ritwik Vatsyayan, Shadi A. Dayeh, Adam J. Engler
Journal: Biomaterials (2023)
FetusMapV2: Enhanced fetal pose estimation in 3D ultrasound
Authors: Chaoyu Chen, Xin Yang, Yuhao Huang, Wenlong Shi, Yan Cao, Mingyuan Luo, Xindi Hu, Lei Zhu, Lequan Yu, Kejuan Yue, Yuanji Zhang, Yi Xiong, Dong Ni, Weijun Huang
Journal: Medical Image Analysis (2023)
Cleaved SPP1-rich extracellular vesicles from osteoclasts promote bone regeneration via TGFβ1/SMAD3 signaling
Authors: Abdullah Faqeer, Mengzhen Wang, Gulzar Alam, Arshad Ahmed Padhiar, Dexiu Zheng, Zhiming Luo, Irene Shuping Zhao, Guangqian Zhou, Jeroen J.J.P. van den Beucken, Huanan Wang, Yang Zhang
Journal: Biomaterials (2023)

Bone remodeling is a tightly coupled process between bone forming osteoblasts (OBs) and bone resorbing osteoclasts (OCs) to maintain bone architecture and systemic mineral homeostasis throughout life. However, the mechanisms responsible for the coupling between OCs and OBs have not been fully elucidated. Herein, we first validate that secreted extracellular vesicles by osteoclasts (OC-EVs) promote osteogenic differentiation of mesenchymal stem cells (MSCs) and further demonstrate the efficacy of osteoclasts and their secreted EVs in treating tibial bone defects. Furthermore, we show that OC-EVs contain several osteogenesis-promoting proteins as cargo. By employing proteomic and functional analysis, we reveal that mature osteoclasts secrete thrombin cleaved phosphoprotein 1 (SPP1) through extracellular vesicles which triggers MSCs osteogenic differentiation into OBs by activating Transforming Growth Factor β1 (TGFβ1) and Smad family member 3 (SMAD3) signaling. In conclusion, our findings prove an important role of SPP1, present as cargo in OC-derived EVs, in signaling to MSCs and driving their differentiation into OBs. This biological mechanism implies a paradigm shift regarding the role of osteoclasts and their signaling toward the treatment of skeletal disorders which require bone formation.
Unleashing the healing potential: Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery
Authors: Liangwei Si, Xiong Guo, Hriday Bera, Yang Chen, Fangfang Xiu, Peixin Liu, Chunwei Zhao, Yasir Faraz Abbasi, Xing Tang, Vito Foderà, Dongmei Cun, Mingshi Yang
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management. In this study, a greater efficacy in burn wound healing and the associated mechanisms of α-lactalbumin (ALA) based electrospun nanofibrous scaffolds (ENs) as compared to other regenerative protein scaffolds were established. Bovine serum albumin (BSA), collagen type I (COL), lysozyme (LZM) and ALA were separately blended with poly(ε-caprolactone) (PCL) to fabricate four different composite ENs (LZM/PCL, BSA/PCL, COL/PCL and ALA/PCL ENs). The hydrophilic composite scaffolds exhibited an enhanced wettability and variable mechanical properties. The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs. As compared to PCL ENs and other composite scaffolds, the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen sponge
Risk of haematologic cancers among individuals tested for Borrelia burgdorferi antibodies, and Borrelia burgdorferi seropositive individuals: a nationwide population-based matched cohort study
Authors: Malte M. Tetens, Lars Haukali Omland, Ram Dessau, Svend Ellermann-Eriksen, Nanna S. Andersen, Charlotte Sværke Jørgensen, Christian Østergaard, Jacob Bodilsen, Kirstine K. Søgaard, Jette Bangsborg, Alex Christian Nielsen, Jens Kjølseth Møller, Ming Chen, Carsten Utoft Niemann, Anne-Mette Lebech, Niels Obel
Journal: Clinical Microbiology and Infection (2023)

In a nationwide, matched cohort study, we aimed to investigate risks of haematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals.
Factors associated with time to surgical treatment for dermatofibrosarcoma protuberans
Authors: Caroline M. Wilkowski, Jessica B. Brown-Korsah, Raghav Tripathi, Jeremy S. Bordeaux
Journal: Journal of the American Academy of Dermatology (2023)

To the Editor: Dermatofibrosarcoma protuberans (DFSP) is an infiltrative, locally aggressive cutaneous malignancy with high local recurrence rates and often extensive local invasion. Early treatment of DFSP may play a role in minimizing its associated morbidity.1 However, little is known regarding predictors of time to treatment for DFSP. Our objective is to investigate factors associated with time from diagnosis to definitive surgical treatment (TTDS) for patients with DFSP.
Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies: A nationwide cohort study
Authors: Celeste J. Eggermont, Loes M. Hollestein, Andrya Hollatz, Marieke Louwman, Antien L. Mooyaart, Tamar Nijsten, Marlies Wakkee
Journal: Journal of the American Academy of Dermatology (2023)

There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC.
Metabolic Dysfunction-Associated Steatotic Liver Disease Facilitates Hepatitis B Surface Antigen Seroclearance and Seroconversion
Authors: Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chi-Ling Chen, Shih-Jer Hsu, Chen-Hua Liu, Sih-Han Liao, Chun-Ming Hong, Ting-Yuan Lan, Hung-Chih Yang, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao
Journal: Clinical Gastroenterology and Hepatology (2023)
Snare Tip Soft Coagulation vs Argon Plasma Coagulation vs No Margin Treatment After Large Nonpedunculated Colorectal Polyp Resection: a Randomized Trial
Authors: Douglas K. Rex, Gregory B. Haber, Mouen Khashab, Amit Rastogi, Muhammad K. Hasan, Christopher J. DiMaio, Nikhil A. Kumta, Satish Nagula, Stuart Gordon, Firas Al-Kawas, Jerome D. Waye, Hadie Razjouyan, Charles E. Dye, Matthew T. Moyer, Jeremiah Shultz, Rachel E. Lahr, Poi Yu Sofia Yuen, Rebekah Dixon, LaKeisha Boyd, Heiko Pohl
Journal: Clinical Gastroenterology and Hepatology (2023)

<h3>Background & Aims</h3> Thermal treatment of the defect margin after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions reduces the recurrence rate. Both snare tip soft coagulation (STSC) and argon plasma coagulation (APC) have been used for thermal margin treatment, but there are few data directly comparing STSC with APC for this indication. <h3>Methods</h3> We performed a randomized 3-arm trial in 9 US centers comparing STSC with APC with no margin treatment (control) of defects after EMR of colorectal nonpedunculated lesions ≥15 mm. The primary end point was the presence of residual lesion at first follow-up. <h3>Results</h3> There were 384 patients and 414 lesions randomized, and 308 patients (80.2%) with 328 lesions completed ≥1 follow-up. The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% with control subjects (no margin treatment). The odds of residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (<i>P</i> = .001 and <i>P</i> = .01, respectively). The difference in odds was not significant between STSC and APC. STSC took less time to apply than APC (median, 3.35 vs 4.08 minutes; <i>P</i> = .019). Adverse event rates were low, with no difference between arms. <h3>Conclusions</h3> In a randomized trial STSC and APC were each superior to no thermal margin treatment after EMR. STSC was faster to apply than APC. Because STSC also results in lower cost and plastic waste than APC (APC requires an additional device), our study supports STSC as the preferred thermal margin treatment after colorectal EMR. (Clinicaltrials.gov, Number NCT03654209.)
Nano-bio interactions in mRNA nanomedicine: Challenges and opportunities for targeted mRNA delivery
Authors: Qimanguli Saiding, Zhongyang Zhang, Shuying Chen, Fan Xiao, Yumeng Chen, Yongjiang Li, Xueyan Zhen, Muhammad Muzamil Khan, Wei Chen, Seyoung Koo, Na Kong, Wei Tao
Journal: Advanced Drug Delivery Reviews (2023)
Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure
Authors: Jiawen Zhou, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Zhiwen Fan, Jie Li, Yong Xu, Zilong Li
Journal: Acta Pharmaceutica Sinica B (2023)

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.
Impact of dupilumab on patch test results and allergic contact dermatitis: A prospective multicenter study
Authors: Sarah Bocquel, Angèle Soria, Nadia Raison-Peyron, Antoine Badaoui, Pierre Marcant, Corina Bara, Françoise Giordano-Labadie, Emmanuelle Amsler, Brigitte Milpied, Juliette Delaunay, Anne-Sophie Darrigade, Pauline Pralong, Claire Boulard, Marie-Christine Ferrier Le Bouedec, Marie Tauber, Justine Pasteur, Aude Valois, Aurélie Le Thuaut, Marie-Noëlle Crépy, Claire Bernier
Journal: Journal of the American Academy of Dermatology (2023)
Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma
Authors: Tahereh Setayesh, Ying Hu, Farzam Vaziri, Xin Chen, Jinping Lai, Dongguang Wei, Yu-Jui Yvonne Wan
Journal: Acta Pharmaceutica Sinica B (2023)

This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment.
Thirty Years of Progress Thanks to the <i>RET</i> Oncogene
Authors: Frederic Castinetti, Francoise Borson-Chazot
Journal: New England Journal of Medicine (2023)

Although medullary thyroid cancer accounts for less than 5% of thyroid cancers, it deserves attention because of its phenotypic heterogeneity, its often aggressive behavior, and the long-term lack of curative postoperative treatment. In 25% of cases, medullary thyroid cancer may be part of a rare genetic tumor syndrome, multiple endocrine neoplasia type 2 (MEN-2). In 1993, mutations in the RET (rearranged during transfection) proto-oncogene were identified by Mulligan and colleagues as responsible for MEN-2.1 It is therefore quite a coincidence that on the 30th anniversary of the discovery of RET, the first drug specifically targeting this pathway is now recognized . . .
Amivantamab plus Chemotherapy in NSCLC with <i>EGFR</i> Exon 20 Insertions
Authors: Caicun Zhou, Ke-Jing Tang, Byoung Chul Cho, Baogang Liu, Luis Paz-Ares, Susanna Cheng, Satoru Kitazono, Muthukkumaran Thiagarajan, Jonathan W. Goldman, Joshua K. Sabari, Rachel E. Sanborn, Aaron S. Mansfield, Jen-Yu Hung, Michael Boyer, Sanjay Popat, Josiane Mourão Dias, Enriqueta Felip, Margarita Majem, Mahmut Gumus, Sang-we Kim, Akira Ono, John Xie, Archan Bhattacharya, Trishala Agrawal, S. Martin Shreeve, Roland E. Knoblauch, Keunchil Park, Nicolas Girard
Journal: New England Journal of Medicine (2023)

Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (
First-Line Selpercatinib or Chemotherapy and Pembrolizumab in <i>RET</i> Fusion–Positive NSCLC
Authors: Caicun Zhou, Benjamin Solomon, Herbert H. Loong, Keunchil Park, Maurice Pérol, Edurne Arriola, Silvia Novello, Baohui Han, Jianying Zhou, Andrea Ardizzoni, M. Perez Mak, Fernando C. Santini, Yasir Y. Elamin, Alexander Drilon, Jürgen Wolf, Nalin Payakachat, Minji K. Uh, Deborah Rajakumar, Hongmei Han, Tarun Puri, Victoria Soldatenkova, A. Bence Lin, Boris K. Lin, Koichi Goto
Journal: New England Journal of Medicine (2023)

Selpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced RET fusion–positive non–small-cell lung cancer (NSCLC) in a nonrandomized phase 1–2 study. Download a PDF of the Research Summary. In a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat–pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were assigned to the control group) and the overall intention-to-treat population. Crossover from the control group to the selpercatinib group was allowed if disease progression as assessed by blinded independent central review occurred during receipt of control treatment. In total, 212 patients underwent randomization in the intention-to-treat–pembrolizumab population. At the time of the preplanned interim efficacy analysis, median progression-free survival was 24.8 months (95% confidence interval [CI], 16.9 to not estimable) with selpercatinib and 11.2 months (95% CI, 8.8 to 16.8) with control treatment (hazard ratio for progression or death, 0.46; 95% CI, 0.31 to 0.70; P<0.001). The percentage of patients with an objective response was 84% (95% CI, 76 to 90) with selpercatinib and 65% (95% CI, 54 to 75) with control treatment. The cause-specific hazard ratio for the time to progression affecting the central nervous system was 0.28 (95% CI, 0.12 to 0.68). Efficacy results in the overall intention-to-treat population (261 patients) were similar to those in the intention-to-treat–pembrolizumab population. The adverse events that occurred with selpercatinib and control treatment were consistent with those previously reported. Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion–positive NSCLC. (Funded by Eli Lilly and others; ClinicalTrials.gov number, NCT04194944.) QUICK TAKE VIDEO SUMMARYFirst-Line Selpercatinib in RET Fusion–Positive NSCLC 01:52
Neoadjuvant cemiplimab and surgery for stage II–IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study
Authors: Neil D Gross, David M Miller, Nikhil I Khushalani, Vasu Divi, Emily S Ruiz, Evan J Lipson, Friedegund Meier, Yungpo Bernard Su, Paul L Swiecicki, Jennifer Atlas, Jessica L Geiger, Axel Hauschild, Jennifer H Choe, Brett G M Hughes, Dirk Schadendorf, Vishal A Patel, Jade Homsi, Janis M Taube, Annette M Lim, Renata Ferrarotto, Suk-Young Yoo, Melissa Mathias, Hyunsil Han, Frank Seebach, Israel Lowy, Matthew G Fury, Danny Rischin
Journal: The Lancet Oncology (2023)
Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma
Authors: Jessica C. Hassel, Sophie Piperno-Neumann, Piotr Rutkowski, Jean-Francois Baurain, Max Schlaak, Marcus O. Butler, Ryan J. Sullivan, Reinhard Dummer, John M. Kirkwood, Marlana Orloff, Joseph J. Sacco, Sebastian Ochsenreither, Anthony M. Joshua, Lauris Gastaud, Brendan Curti, Josep M. Piulats, April K.S. Salama, Alexander N. Shoushtari, Lev Demidov, Mohammed Milhem, Bartosz Chmielowski, Kevin B. Kim, Richard D. Carvajal, Omid Hamid, Laura Collins, Koustubh Ranade, Chris Holland, Constance Pfeiffer, Paul Nathan
Journal: New England Journal of Medicine (2023)

Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.
A Critical Assessment of Diagnostic Criteria for the Tall Cell Subtype of Papillary Thyroid Carcinoma—How Much? How Tall? And When Is It Relevant?
Authors: John Turchini, Talia L. Fuchs, Angela Chou, Loretta Sioson, Adele Clarkson, Amy Sheen, Leigh Delbridge, Anthony Glover, Mark Sywak, Stan Sidhu, Anthony J. Gill
Journal: Endocrine Pathology (2023)

Tall cell papillary thyroid carcinoma (TC-PTC) is considered adverse histology. However, previous studies are confounded by inconsistent criteria and strong associations with other adverse features. It is therefore still unclear if TC-PTC represents an independent prognostic factor in multivariate analysis and, if it does, what criteria should be employed for the diagnosis. We retrospectively reviewed 487 PTCs from our institution (where we have historically avoided the prospective diagnosis of TC-PTC) for both the height of tall cells (that is if the cells were two, or three, times as tall as wide) and the percentage of tall cells. On univariate analysis, there was significantly better disease free survival (DFS) in PTCs with no significant tall cell component (< 30%) compared to PTCs with cells two times tall as wide (p = 0.005). The proportion of tall cells (30-50% and > 50%) was significantly associated with DFS (p = 0.012). In a multivariate model including age, size, vascular space invasion, and lymph node metastasis, the current WHO tall cell criteria, met by 7.8% of PTCs, lacked statistical significance for DFS (p = 0.519). However, in the subset of tumours otherwise similar to the American Thyroid Association (ATA) guidelines low-risk category, WHO TC-PTC demonstrated a highly significant reduction in DFS (p = 0.004). In contrast, in intermediate to high-risk tumours, TC-PTC by WHO criteria lacked statistical significance (p = 0.384). We conclude that it may be simplistic to think of tall cell features as being present or absent, as both the height of the cells (two times versus three times) and the percentage of cells that are tall have different clinical significances in different contexts. Most importantly, the primary clinical significance of TC-PTC is restricted to PTCs that are otherwise low risk by ATA guidelines.